Antithrombotics at the end-of-life pose a clinical challenge where indication-specific time-to-benefit, bleeding risk, and patient priorities must be reconciled over short prognostic horizons. In this review of the literature, we found that a substantial number of individuals remain on anticoagulants and antiplatelet therapy till the point of death. Prospective ultrasound surveillance studies show a high baseline incidence of asymptomatic proximal deep vein thrombosis at admission but a low short-term incidence of new events during typical hospice stays. Additionally, large home palliative cohorts suggest that deprescribing anticoagulants does not increase clinical thrombosis and may reduce bleeding and facilitate home death. Bleeding on antithrombotics is also common in the last months of life. Clinically relevant bleeding occurs in up to 1 in 10, and fatal hemorrhage has been reported. Cancer-specific factors, chronic or end-stage kidney disease, cytopenias, and drug interactions heighten the risks. Where anticoagulation is pursued, the choice of agent and route should reflect swallowing, nutrition, renal or hepatic function, monitoring capacity, and reversal intent. Structured, shared decision making and proactive deprescribing when benefits no longer outweigh harms are central.

Background: Decision making about antithrombotic therapy (ATT) in patients with advanced cancer near the end of life is fraught with clinical uncertainty and can significantly affect care. Despite its importance and complexity, ATT is often deprioritized or guided by legacy prescribing and monitoring patterns. Management spans multiple specialties, with roles and responsibilities frequently blurred. Clinicians’ perspectives remain largely underexplored, which are crucial to inform improved care models. Objectives: This study explores clinicians’ experiences of current practice of continuing and deprescribing ATT in patients with advanced cancer at the end of life. Methods: Qualitative methodology using semistructured interviews with clinicians involved in ATT management at the end of life, across Denmark, France, Spain, and the United Kingdom. Data were analyzed using Framework Analysis. Results: Eighty clinicians across a range of specialties were interviewed. Two major themes were generated: (1) balancing complexities in ATT management: clinicians reported several challenges, from ambiguity surrounding roles and responsibilities, delicacy around timing, and variance in risk perceptions of ATT, balanced with patient preferences; and (2) culture of continuation: clinicians described a general and ATT-specific culture of continuation and reported a passivity in relation to ATT review. Conclusion: The management of ATT in this context is multifaceted, influenced by many competing factors. These complexities need to be understood and addressed to support decision making related to ATT at the end of life.

PURPOSE:It is unclear whether patients with cancer continue to benefit from antithrombotic therapy (ATT) during the last phase of life. We estimated the incidences of ATT discontinuation, bleeding, and venous thromboembolic (VTE) and arterial thromboembolic (ATE) events among patients with cancer during the last phase of life. METHODS:We included patients aged ≥18 years with cancer during the period 2018 to 2022 at the time a reimbursement claim for general practitioner (GP) palliative care was made. We manually identified ATT discontinuation, along with reasons, and the incidences of bleeding events, VTE events, and ATE events in free-text reports of routine primary care consultations until death. RESULTS:Among the 2,860 included patients, 32.5% used ATT at the index date. The median follow-up was 43 (interquartile range [IQR] 14-190) days for ATT users and 42 (IQR 13-149) days for nonusers. During follow-up, 22.1% of ATT users discontinued ATT, with a median of 8 (IQR 3-26) days before death. The most common reason for discontinuation was recognition of the terminal phase (22.9%). Bleeding occurred for 28.5% (95% CI, 25.7%-31.5%) of ATT users and 22.0% (95% CI, 20.2%-23.9%) of nonusers. Venous thromboembolic events occurred for 3.1% (95% CI, 2.2%-4.4%) of ATT users and 3.0% (95% CI, 2.3%-3.9%) of nonusers, and ATE events occurred for 2.5% (95% CI, 1.7%-3.7%) of ATT users and 1.9% (95% CI, 1.4%-2.6%) nonusers. DISCUSSION:One-third of patients with cancer used ATT at the initiation of GP palliative care, with most continuing treatment until death or discontinuing shortly before death. Bleeding events largely outnumbered ATE and VTE events among both ATT users and non-users. These findings provide new insights into ATT management by GPs and inform future research on optimizing ATT use for patients with cancer during the last phase of life.

INTRODUCTION:To develop a European shared decision-support tool (SDST), a two-round Delphi process was used to achieve consensus on aspects relating to the antithrombotic therapy (ATT) deprescribing discussions and process in end-of-life cancer patients. METHODS:Conducted between September 2024 and March 2025, the Delphi survey was developed by a multidisciplinary 24-member steering committee (SC), including medical specialists in oncology, hematology, palliative care, primary care, geriatrics, and vascular medicine. The survey involved 188 experts from these specialties across eight European countries. Consensus was defined with pooled items as ≥70 % agreement with a final decision by the SC. Themes covered deprescribing timing, stakeholders, reassessment and clinical drivers of patients with ATT, SDST, and choice of outcomes for a randomized controlled trial (RCT) to evaluate the SDST. RESULTS:Round 1 reached consensus for seven pooled questions (37 %), especially the reassessment of ATT deprescribing. Considering these results, the SC reformulated round 2 to reduce ambiguity and move toward consensus. The SC made the final decision. Three medical specialties should be involved in ATT deprescribing: palliative care specialists, oncologists, and general practitioners after a triggering circumstance such as clinical triggers or at 3-month prognosis. For the SDST design, the findings confirmed that this tool would be meaningful to clinicians. Eleven predefined outcomes were selected for a future RCT. CONCLUSION:These results succeeded in shaping the content of the future SDST and mapping its useability in palliative care clinical pathways across Europe, with the perspective to support informed decision-making, reduce complications, and improve quality of life in this population.

Objectives VALTIVE1 is a multi-centre, single-arm, non-interventional biomarker study for patients with advanced ovarian cancer. Plasma samples (Tie2 concentration) are collected to detect vascular control in tumours during standard treatment with chemotherapy and bevacizumab. This qualitative study embedded in VALTIVE1 aimed to assess the acceptability and feasibility of a potential VALTIVE2 trial. It explored the participants’ perceptions of the study and treatments and how they might feel if bevacizumab were discontinued based on the results from the biomarker test.Design This qualitative study used semi-structured telephone interviews, which were analysed using deductive and inductive thematic analysis.Settings Cancer treatment sites in the UK.Participants Participants recruited to VALTIVE1 were invited to take part in qualitative interviews. 11 female participants took part from four clinical sites.Results Participants reported that they experienced side effects attributed to bevacizumab, including stiffness, pain, fatigue, nose bleeds and muscle aches. Participants felt that combining chemotherapy and bevacizumab may have increased the severity of the side effects they experienced. Most participants felt that it was acceptable, if not preferable, to be allocated to a group in a future VALTIVE2 study where bevacizumab may be discontinued according to the results from the biomarker test. A clear preference of participants was to be informed of the biomarker test results, health status and treatment side effects.Conclusion A future trial should consider ensuring all participants have access to test results, as participants indicated a preference to know whether bevacizumab was working and to discontinue bevacizumab if it had not prevented tumour growth based on the biomarker results. Comprehensive and ongoing information and support regarding treatment side effects should be provided to all participants throughout their cancer pathways and trials.Trial registration number NCT04523116.

All of us will one day die. For most of us, death will be anticipated, usually following a period of ill health. The opportunity to anticipate and manage clinical conditions associated with the agonal process is an essential part of advance care planning. Guidelines exist for the palliation of most symptomatic events at the end of life, although many recommendations are based on low-quality evidence or consensus. Furthermore, when potentially practice-changing data emerge, there is an inevitable lag time before clinical practice changes. In this paper, we shall discuss the management of three challenging scenarios faced by teams looking after patients at the end of life: delirium, terminal haemorrhage and noisy upper airway secretions. We aim to critically evaluate the utility of current evidence, pharmacological and non-pharmacological, and how it translates into clinical practice.

Anti-thrombotic therapy (ATT) in cancer patients approaching the end of life presents significant clinical challenges, balancing thrombotic and bleeding risks. This study analysed ATT prescribing patterns and associated outcomes in patients diagnosed with poor prognosis cancer, defined as cancer diagnoses associated with a 1-year life expectancy, using the Welsh national Secure Anonymised Information Linkage Databank. Retrospective cohort study of adults in Wales diagnosed with poor prognosis cancer between 2013 and 2021, following up patients from cancer diagnosis until death, end of follow-up or study end (31 December 2021). Outcomes included ATT discontinuation, bleeding and thromboembolic events in secondary care. We identified a cohort of 25 783 adults with a median survival of 145 days. Of these, 32% were receiving ATT at diagnosis, with 77% continuing until death. One-year cumulative incidence of ATT discontinuation was 19% (95% CI: 18%-20%). The 1-year cumulative incidence of bleeding was 3.2% (95% CI: 3.0%-3.4%) and of thromboembolic events was 5.3% (95% CI: 5.0%-5.6%). ATT was prevalent at cancer diagnosis and discontinuation before death was uncommon. The management of ATT is complex in patients with advanced cancer and there is a need for clearer guidance on appropriate discontinuation strategies as well as when to continue these medicines.

Background The increasing use of computed tomography pulmonary angiography to investigate patients with suspected pulmonary embolism has led to an increase in diagnosis of small subsegmental pulmonary embolism, which is rarely detectable with nuclear medicine-based imaging, the standard imaging modality prior to the development of computed tomography pulmonary angiography. The case fatality of pulmonary embolism has fallen in line with the increase in subsegmental pulmonary embolism diagnoses from computed tomography pulmonary angiography suggesting that we may be over-diagnosing pulmonary embolism (i.e. we may be diagnosing mild forms of pulmonary embolism which may not need any treatment). Given that full anticoagulation has significant side effects of bleeding and subsegmental pulmonary embolism was not commonly diagnosed previously with nuclear medicine imaging (and therefore left predominantly untreated prior to computed tomography pulmonary angiography scanning), there is growing equipoise about the value of full anticoagulation for patients with subsegmental pulmonary embolism. Methods We tried to undertake an open randomised trial with blinded end-point adjudication that recruited patients diagnosed with subsegmental pulmonary embolism without evidence of thrombus in the leg veins, termed ‘isolated subsegmental pulmonary embolism’. We allocated patients with isolated subsegmental pulmonary embolism to either continuing with at least 3 months of full-dose anticoagulation (standard care) or stopping anticoagulation completely, unless they had a temporary hospital admission where prophylactic (i.e. preventative doses) of anticoagulation is standard practice. In addition, we interviewed patients and clinicians about their views on stopping anticoagulation for isolated subsegmental pulmonary embolism which would be a substantial change from current practice. We planned to assess the accuracy of isolated subsegmental pulmonary embolism diagnoses from computed tomography pulmonary angiographies. Results The trial was stopped prematurely due to low recruitment. This was due to a combination of insufficient trial sites, problems with identifying patients who were suitable to be recruited at the time of acute assessment in hospital, the impact of COVID-19 on research infrastructure and a lower prevalence than had been predicted based on published studies. Our interview study showed that the intervention (i.e. changing practice to stopping treatment) is feasible, although there were concerns raised about safety, which a trial would be needed to address. We did not have sufficient trial participants to determine accuracy of initial isolated subsegmental pulmonary embolism diagnoses. Conclusion Although we were not able to answer the question of whether it is clinically effective and cost-effective to stop anticoagulating patients with isolated subsegmental pulmonary embolism, we developed a protocol which can be used by future trialists who can successfully attract funding to address this research question, which remains important and an ongoing uncertainty for clinicians and patients. Future work Trialists attempting to answer this research question should plan for longer recruitment times and ensure there is sufficient resource for a large number of recruiting centres. Limitations There were insufficient recruits to progress from the pilot phase to the full STOPAPE trial. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128073.

INTRODUCTION:Patients with cancer are at increased risk of thrombotic complications from both the disease and its treatments, with antithrombotic therapy (ATT) usually continued in the last phase of life where the benefit is less clear and there is high risk of harms. Physiological changes toward the end of life increase the risk that ATT will cause serious bleeding events, but discussion between clinicians and patients of ATT risks and benefits is sub-optimal. This realist synthesis explores shared decision-making (SDM) to: (a) provide insights into why prescribing continues in end-of-life care; (b) build a conceptual platform for optimizing ATT prescribing for persons living with cancer towards end-of-life. METHODS AND FINDINGS:We conducted a realist synthesis using context-mechanism-outcome configurations and 'if…then' statements. A total of 17,036 citations identified across 10 databases (Medline, EMBASE, APA PsycInfo, CINAHL Complete, CDSR, CENTRAL, EPISTEMONIKOS, Web of Science Core Collection, Assia, Google Scholar). Ninety-one papers included following reverse chronology quota record screening (from: database searches (n = 56), consortium experts (n = 35)). Included papers: quantitative (n = 40), qualitative (n = 17), mixed-methods (n = 2), evidence syntheses (n = 16), commentaries (n = 9), case reports (n = 7). Exclusion criteria: persons <18 years, non-English language, not focused on SDM or deprescribing in palliative care. An analytic appraisal journal was used with realist logic to synthesize insights from included papers (contents from 43/91 included in this paper). The concept of 'prescribing inertia' was used to formulate explanatory theories about clinician reluctance to deprescribe and the mechanisms underpinning SDM, including (a) the meaning medications have to end-of-life patients (e.g., 'life preserving' or 'symptom management') and public awareness of medications (e.g., high-profile chemotherapy versus low-profile ATT) are determinants of: (i) clinician motivation to engage patients around deprescribing, (ii) patient understanding, volition and participation in SDM; (b) SDM for ATT deprescribing requires sensitive engagement with patients and families without removing positivity around survival and continuing clinician interest in their welfare; (c) multi-disciplinary clinical decision-making about timing and suitability of deprescribing in end-of-life care requires specialized consensus-driven processes and evidence-based decision support tools; (d) if patients are healthy enough, empowerment interventions outside clinical encounters (e.g., health literacy apps) may increase patient and family readiness to engage in deprescribing conversations; (e) organizational investments can facilitate discussion of deprescribing (e.g., improved electronic medical record prompts, clinician communication skills training, data presentation to clinicians of actual ATT risks). Limitations: despite robust screening and selection, the sample of included papers does not reflect the entirety of eligible source material and did not include a systematic search for papers focusing on low- and middle-income country countries. CONCLUSION:Implementation of ATT deprescribing is enabled or constrained by (a) the meaning of medications to patients; (b) clinician engagement and understanding; (c) multi-disciplinary clinical decision-making processes (including support tools); (d) patient empowerment; (e) organizational investment. Addressing these multi-level factors, including the development of SDM tools, can address the prescribing inertia that may cause devastating impacts on patients and their families as well as moral distress amongst healthcare staff. This study was performed as part of the Horizon-Europe funded SERENITY project.

Background Developing and implementing interventions that change clinical practice can be challenging and complex. Such interventions can be particularly difficult when attempting to change established behaviours and practices. While extensive literature on implementation of interventions that focus on changing clinical practice exists, understanding of the difficulties involved in implementing interventions that go against accepted clinical practice is limited. Objectives To describe the challenges involved in delivering a complex intervention that goes against established clinical practice, using a clinical trial assessing the balance of benefits and risks of withholding anticoagulation for subsegmental pulmonary embolism as an example. Design and methods This study draws from a process evaluation conducted as part of a clinical trial. The evaluation utilised semistructured interviews with patients and clinicians during the trial’s internal pilot phase to investigate the acceptability of withholding anticoagulant medication and participants’ experiences within the trial. The data were analysed using the framework method. Setting and participants Eight patients with subsegmental pulmonary embolism (six females and two males) and three acute care clinicians (two males and one female) from five trial sites were interviewed. Results Our findings indicated that factors such as clinician equipoise, discomfort with certain patient characteristics, and effective patient communication are closely connected and significantly impact both the process of changing clinical practice and the conduct of the trial. Clinicians faced difficulties in approaching eligible patients for trial participation, especially when a diagnosis and treatment plan had already been provided by another clinician. The tension between maintaining clinical equipoise and addressing the needs of unwell patients further complicated decisions, particularly when withholding anticoagulation in those with severe symptoms or multiple comorbidities. Communication about the risks and benefits of non-medication strategies for pulmonary embolism was also challenging, with concerns about undermining patient trust. Patients, on the other hand, expressed considerable anxiety about not receiving anticoagulants, with their perspectives on study participation and treatment heavily influenced by their prior health experiences and ongoing medical conditions. The active involvement of clinicians in the consent process had a positive effect on patients’ perceptions and experiences, with many feeling reassured in knowing they could contact clinical staff if needed. Limitations Small sample size of patients and clinicians across limited study sites; single method of data collection. Conclusions Our results highlight the multifaceted challenges when attempting to conduct studies that challenge accepted practices and norms. These complexities are deeply intertwined, influencing both clinical decision-making and patient recruitment for those studies. Future work Future research should focus on developing strategies to help clinicians maintain equipoise and communicate the risks and benefits of interventions, while also deepening the understanding of patients’ experiences and perceptions to enhance recruitment strategies. Ethical approval Wales REC 6, Reference: 20/WA/0256, approved 30 September 2020. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128073.

Background: Data on risks and benefits of long-term anticoagulants in patients with a life-limiting disease are limited. This cohort study aims to describe (dis)continuation of anticoagulants and incidences of bleeding and thromboembolic events in vitamin K antagonist (VKA) users with a life-limiting disease. Methods: Data from five Dutch anticoagulation clinics were linked to data from Statistics Netherlands and the Netherlands Cancer registry. Prevalent VKA users diagnosed with a pre-specified life-limiting disease between 01/01/2013 and 31/12/2019 were included and followed until 31/12/2019. Hospitalization data were used to identify bleeding and thromboembolic events. Cumulative incidences of anticoagulant discontinuation were calculated, accounting for death as competing risk, and event rates were determined for both anticoagulant exposed and unexposed person-years (PYs). Results: Among 18,145 VKA users (median age 81 years, 49% females, median survival time 2.03 years), the most common life-limiting diseases were heart disease (60.0%), hip fracture (18.1%), and cancer (13.5%). One year after diagnosis, the cumulative incidence of anticoagulant discontinuation was 14.0% (95%CI: 13.5-14.6). Over 80% of patients continued anticoagulant therapy until the last month before death, with median 14 days between discontinuation and death. Event rates per 100 PYs (95%CI) were comparable during anticoagulant use and after discontinuation for bleeding 2.6 (2.4-2.8) versus 2.1 (1.5-2.8); venous thromboembolism 0.2 (0.1-0.2) versus 0.4 (0.2-0.7); and arterial thromboembolism 3.1 (2.9-3.3) versus 3.3 (2.6-4.2). Conclusion: Most VKA users with a life-limiting disease continued anticoagulant treatment during their last phase of life, with similar rates of bleeding and thromboembolic events during use and after discontinuation.

BACKGROUND Venous thromboembolism (VTE) is a potentially preventable serious complication in patients with lung cancer undergoing thoracic operation. We examined the risk and timing of VTE after surgery for primary non -small cell lung cancer (NSCLC). METHODS All patients undergoing operation for NSCLC in Denmark between 2003 and 2021 were identified in the Danish Lung Cancer Registry. VTE events in the year after operation were assessed by stage, patient characteristics, and surgical procedure. RESULTS We identified 13,197 patients who underwent operation for NSCLC in 2003 to 2021 (mean age, 67.6 years; 50% female); 10,524 (79.7%) had stage I -II NSCLC, and 2673 (20.3%) had stage III -IV. During 1 -year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person -years and an absolute risk of 3.3% (95% CI, 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I vs 3.9% for stage IV) but varied little by pathologic type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%; 95% CI, 3.2-6.9), followed by pneumonectomy (3.5%; 95% CI, 2.3-5.0). The hazard of VTE was highest during the first 3 months after operation, after which it declined. For stage IV cancer, hazards increased again after 6 months. At 1 year, all -cause death was 12.6% (95% CI, 12.0%-13.1%). CONCLUSIONS VTE developed in 3.3% of patients undergoing operation for NSCLC, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections. (Ann Thorac Surg 2024;117:289-96) (c) 2024 by The Society of Thoracic Surgeons. Published by Elsevier Inc.

ObjectivesVenous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non-small cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB-C, and stage IV NSCLC according to received cancer treatments.Materials and MethodsA nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen-Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy.ResultsAmong the 3,475 patients with stage IIIA, 4,047 with stage IIIB-C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first six months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB-C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%) and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis.ConclusionVTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial six months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC.Micro abstractThis nationwide cohort study highlights the significant risk of VTE in patients undergoing cancer therapies for NSCLC. The 1-year risk of VTE was highest within the initial six months of treatment and demonstrated substantial variability on cancer stage and the specific treatments received.These findings emphasize the importance of a nuanced risk assessment tailored to both cancer stage and the specific cancer therapies employed. Such insights contribute to the ongoing efforts to optimize patient care.